A method for treating conditions associated with thalamocortical dysrhythmia. The method includes applying transcranial low voltage electrical stimulation (TLVES) therapy or transcranial magnetic stimulation (TMS) therapy to a patient in need thereof, and administering to the patient a dissociative anesthetic during the TLVES therapy or the TMS therapy. A number of conditions including tinnitus, depression and pain can be treated with TLVES or TMS in combination with the dissociative anesthetic, such as an NMADR inhibitor, including ketamine.

The invention provides anti-oncostatin M receptor-β (OSMR) antigen binding proteins, e.g., antibodies and functional fragments, derivatives, muteins, and variants thereof. OSMR antigen binding proteins interfere with binding of OSM and/or IL-31 to OSMR. In some embodiments, anti-OSMR antigen binding proteins are useful tools in studying diseases and disorders associated with OSMR and are particularly useful in methods of treating diseases and disorders associated with OSMR and binding of OSM and/or IL-31 to OSMR.

The present invention provides for a process for preparing liposomes, lipid discs, and other lipid nanoparticles using a multi-port manifold, wherein the lipid solution stream, containing an organic solvent, is mixed with two or more streams of aqueous solution (e.g., buffer). In some aspects, at least some of the streams of the lipid and aqueous solutions are not directly opposite of each other. Thus, the process does not require dilution of the organic solvent as an additional step. In some embodiments, one of the solutions may also contain an active pharmaceutical ingredient (API). This invention provides a robust process of liposome manufacturing with different lipid formulations and different payloads. Particle size, morphology, and the manufacturing scale can be controlled by altering the port size and number of the manifold ports, and by selecting the flow rate or flow velocity of the lipid and aqueous solutions.

The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands of the NR2B receptor and may be useful for the treatment of various disorders of the central nervous system.

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The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.

The present invention relates to a compound represented by the formula (I) or a salt thereof.

##STR00001##

wherein each symbol is as described in the specification, or a salt thereof.

The present invention relates to low volume intravenous injections of paracetamol or its pharmaceutically acceptable salt and method of preparation thereof. The formulations provide high concentration of paracetamol or its pharmaceutically acceptable salt in a solvent system of the present invention which can be administered not only through intra-muscular & intravenous infusion route but also suitable for slow IV bolus administration after dilution with aqueous fluids to final volume of not more than 20 ml. These injectable formulations remain stable and are also suitable for administration through slow intravenous route with minimized side effects (such as phlebitis, pain etc.).

Pharmaceutical formulations with a tropomyosin-related kinase inhibitor (“Trk inhibitor”) are disclosed. The pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine in microcrystalline suspension formulations in its monohydrate form, which shows improved characteristics over the anhydrate form, and in extended release formulations. The extended release pharmaceutical formulations comprise 3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-amine-loaded microspheres.

Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P.sup.1 and P.sup.2 are as defined in this disclosure.

A medicinal agent for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation. A compound having antagonistic activity against the EP.sub.4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP.sub.4 receptor for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation.

##STR00001##

Provided is a production method of a thiazole derivative represented by the formula (I), which has an adenosine A.sub.2A receptor antagonistic action and is useful as a therapeutic agent for, for example, Parkinson's disease, sleep disorder, analgesic resistance to opioid, migraine, movement disorder, depression, anxiety disorder and the like. Also provided is a production method of a compound represented by the formula (C), which contains (i) a step of reacting a compound represented by the formula (A) and a compound represented by the formula (B), and the like:

##STR00001##

(wherein R.sup.1 represents furyl, R.sup.4, R.sup.5 and R.sup.6 are the same or different and each represents lower alkyl or aryl, R.sup.2 represents pyridyl or tetrahydropyranyl, and X.sup.1 represents halogen).